This proposal aims to develop techniques to restore sensory hair cells and thus hearing loss in humans. Loss of the sensory hair cells in the Organ of Corti is thought to be a major cause of hearing deficits. In non-mammalian vertebrates that are able of regenerating hair cells after death or loss a first key step is the renewed proliferative capacity of the non-sensory supporting cells. Supporting cell proliferation gives rise to new functioning hair cells after acoustic trauma or ototoxic drugs. Supporting cell proliferation has never been observed in the mammalian organ of Corti, even after hair cell death or the application of growth factors. The Principal Investigator has recently determined that p27kip1, a cyclin/cyclin-dependent kinase inhibitor, is expressed in the supporting cells of mice from birth and in adulthood. Experiments are proposed to test whether deletion of p27 is sufficient to induce the regeneration of hair cells following drug-induced hair cell death. In addition, the Principal Investigator proposes to test whether deletion of p27kip1 can alter the progressive outer hair cell loss observed in C57B/6J mice that is similar to the patterns of hair cell loss observed in age- related hearing loss in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE